Renal Filtration, Transport, and Metabolism of Albumin and Albuminuria

Comper, Wayne D.; Osicka, Tanya M; Russo, Leileata M.

doi:10.1016/b978-012088488-9.50077-2

Cited by 8 publications

(17 citation statements)

References 286 publications

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“…These physicochemical studies have included chromatographic analysis, diffusion analysis, and light scattering analysis [20]. These studies came to the same conclusion-that albumin interaction with negatively charged glycosaminoglycans under physiologic conditions is based primarily on size and not charge.…”

Section: Gsc Of Negatively Charged Transport Probesmentioning

confidence: 97%

Where does albuminuria come from in diabetic kidney disease?

Comper

Russo²

2008

Curr Diab Rep

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The classic mechanism to explain albumin excretion in diabetes has been permeability defects in the glomerular fi lter. However, a new concept has emerged that albuminuria can be explained by the two major pathways the proximal tubular cell uses to process fi ltered albumin. Specifi cally, albumin permeability through the glomerular fi lter is only governed by size selectivity. Most of the fi ltered albumin is retrieved by the proximal tubular cell and returned to the peritubular blood supply. Albuminuria in the nephrotic range would arise from retrieval pathway dysfunction. The small quantities of fi ltered albumin that are not retrieved undergo obligatory lysosomal degradation before urinary excretion as small peptide fragments. This pathway is sensitive to metabolic factors responsible for hypertrophy and fi brosis, particularly molecules such as angiotensin II and transforming growth factor-β1, whose production is stimulated by hyperglycemic environments. Dysfunction in this degradation pathway may lead to albuminuria below the nephrotic range.

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Section: Gsc Of Negatively Charged Transport Probesmentioning

confidence: 97%

Where does albuminuria come from in diabetic kidney disease?

Comper

Russo²

2008

Curr Diab Rep

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“…Accordingly, the initial MPM observations of various cell and kidney functions, including glomerular filtration and tubular processing of substances (6,7,29,54), and cell apoptosis and endocytosis (6), were later followed by quantitative, more complex approaches. These included the quantitative imaging (17) of the singlenephron glomerular filtration rate (SNGFR), red cell velocity in glomerular and peritubular capillaries for blood flow estimations, oscillations in SNGFR and tubular fluid flow, changes in renal concentration-dilution, and the highly debated measurement of the glomerular sieving coefficient of albumin (3,31,39,45,46,52,53). The Molitoris group established the ratiometric measurement of glomerular filtration function using various GFR and plasma markers (61,64,65).…”

Section: Quantitative Imaging Of Kidney Functions In Vivomentioning

confidence: 99%

“…Applications of MPM helped to change several paradigms in renal (patho)physiology. Imaging data have been incorporated into a number of textbooks on kidney function (3,8,41), and MPM videos (30,37,39,40) have been used as visual aid and teaching material in graduate and medical student classrooms worldwide.MPM offers a state-of-the-art imaging technique superior for deep optical sectioning of living tissues. The higher resolution and minimal phototoxicity of this method permit longer time periods of continuous tissue scanning with uses in near realtime imaging of intact organs in vivo.…”

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confidence: 99%

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The first decade of using multiphoton microscopy for high-power kidney imaging

Peti‐Peterdi

Burford

Hackl

2012

American Journal of Physiology-Renal Physiology

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Peti-Peterdi J, Burford JL, Hackl MJ. The first decade of using multiphoton microscopy for high-power kidney imaging. Am J Physiol Renal Physiol 302: F227-F233, 2012. First published October 26, 2011 doi:10.1152/ajprenal.00561.2011In this review, we highlight the major scientific breakthroughs in kidney research achieved using multiphoton microscopy (MPM) and summarize the milestones in the technological development of kidney MPM during the past 10 years. Since more and more renal laboratories invest in MPM worldwide, we discuss future directions and provide practical, useful tips and examples for the application of this still-emerging optical sectioning technology. Advantages of using MPM in various kidney preparations that range from freshly dissected individual glomeruli or the whole kidney in vitro to MPM of the intact mouse and rat kidney in vivo are reviewed. Potential combinations of MPM with micromanipulation techniques including microperfusion and micropuncture are also included. However, we emphasize the most advanced and complex, quantitative in vivo imaging applications as the ultimate use of MPM since the true mandate of this technology is to look inside intact organs in live animals and humans. intravital imaging; juxtaglomerular apparatus; podocyte; two-photon microscopy IT HAS BEEN MORE THAN 10 YEARS since two-or three-photon excitation, collectively called multiphoton microscopy (MPM), was first applied to the study of the living kidney tissue by the Peti-Peterdi-Bell (37, 38) and Dunn-Molitoris groups (6, 42) that pioneered several applications of this powerful new imaging technology. Over the past decade, MPM has provided stunning images and real-time movies of the structure and function of the intact kidney in unparalleled spatial and temporal resolution. Because of the ability of this noninvasive imaging approach to directly visualize dynamic intrarenal processes in vivo and in near real-time without causing tissue damage, MPM has revolutionized renal physiology research and served as the perfect complement to more traditional biological and histological techniques. MPM also opened the door to studying otherwise inaccessible cell types and complex tissue structures like the glomerular podocyte (30, 39) and the juxtaglomerular apparatus (JGA) (37) in their intact environment. Applications of MPM helped to change several paradigms in renal (patho)physiology. Imaging data have been incorporated into a number of textbooks on kidney function (3,8,41), and MPM videos (30,37,39,40) have been used as visual aid and teaching material in graduate and medical student classrooms worldwide.MPM offers a state-of-the-art imaging technique superior for deep optical sectioning of living tissues. The higher resolution and minimal phototoxicity of this method permit longer time periods of continuous tissue scanning with uses in near realtime imaging of intact organs in vivo. MPM has applications far beyond the generation of superior images: dynamic intracellular processes as well as more complex physiological ...

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“…Values for the glomerular sieving coefficient of albumin have ranged from ,0.001 to 0.07 under various physiologic and pathologic conditions using different techniques. 27 Of particular importance has been the use of Munich-Wistar (MW) rats that have surface glomeruli, allowing for direct dynamic visualization, instrumentation, and manipulation. MW Fromter (MWF) rats have many surface glomeruli, have been used in micropuncture studies, and spontaneously develop hypertension and progressive albuminuria beginning by week 8 and increasing to urinary albumin excretion.300 mg/24 hours by week 32.…”

Section: Importance Of Ptc Albumin Reabsorptionmentioning

confidence: 99%

The Proximal Tubule and Albuminuria

Dickson

Wagner

Sandoval

et al. 2014

Journal of the American Society of Nephrology

232

227

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Recent data highlight the role of the proximal tubule (PT) in reabsorbing, processing, and transcytosing urinary albumin from the glomerular filtrate. Innovative techniques and approaches have provided exciting insights into these processes, and numerous investigators have shown that selective PT cell defects lead to significant albuminuria, even reaching nephrotic range in animal models. Thus, the mechanisms of albumin reabsorption and transcytosis are undergoing intense study. Working in concert with megalin and cubilin, a nonselective multireceptor complex that predominantly directs proteins for lysosomal degradation, the neonatal Fc receptor (FcRn) located at the brush border of the apical membrane has been implicated as the "receptor" mediating albumin transcytosis. The FcRn pathway facilitates reabsorption and mediates transcytosis by its pH-dependent binding affinity in endosomal compartments. This also allows for selective albumin sorting within the PT cell. This reclamation pathway minimizes urinary losses and catabolism of albumin, thus prolonging its serum half-life. It may also serve as a molecular sorter to preserve and reclaim normal albumin while allowing "altered" albumin to be catabolized via lysosomal pathways. Here, we critically review the data supporting this novel mechanism. Although the importance of urinary albumin in disease progression is known, the key mechanisms mediating the presence and toxic effects of albuminuria remain to be determined. Recently, the quantitative role of the glomerular filtration barrier (GFB) and the proximal tubule (PT) cell (PTC) in the development of albuminuria has been reexamined. Different lines of evidence, from multiple investigative teams, now suggest that the filtration of albumin, under physiologic conditions, is greater than previously determined. These data suggest an increased clinical role for the PT in minimizing albuminuria through the reabsorption of albumin. Emerging data also suggest that both glomerular permeability and PTCs play fundamental, physiologic, synergistic, interactive, and dynamic roles in the renal handling of albumin. Furthermore, it appears that PTCs, especially in the S1 segment, have specific mechanisms for efficiently and effectively reabsorbing and transcytosing albumin (reclamation). Therefore, the purpose of this review is to describe the emerging data regarding PTC albumin handling and provide a framework for considering future exciting, insightful, and novel studies with direct clinical relevance.This review is not intended to debate the important role of the GFB but to emphasize that the PT should be considered important both under physiologic and pathologic conditions. We believe that glomerular or PTC defects can and do result in proteinuria. Specifically, we outline current data supporting PT uptake of albumin and mechanisms of reabsorption and transcytosis, and we propose a mechanism for intracellular sorting between degradation and transcytotic pathways based on pH-dependent binding. DYSFUNCTIONAL PTCS LE...

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Renal Filtration, Transport, and Metabolism of Albumin and Albuminuria

Cited by 8 publications

References 286 publications

Where does albuminuria come from in diabetic kidney disease?

Where does albuminuria come from in diabetic kidney disease?

The first decade of using multiphoton microscopy for high-power kidney imaging

The Proximal Tubule and Albuminuria

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